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Integrative neuroscience approach to predict ADHD stimulant response.

Despite high rates of prescription, little is known about the long-term consequences of stimulant medication therapy for attention-deficit hyperactivity disorder (ADHD) sufferers. Historically, the clinical use of stimulants for ADHD has been based on trial and error before optimal therapy is reached. Concurrently, scientific research on the mechanism of action of stimulants has influenced neurobiological models of ADHD, but has not always informed their prescription. Whilst the two main stimulant types (methylphenidate and dexamphetamine) have numerous similarities, they also differ (slightly) in mechanism and possibly individual response. A further issue relates to differences in cost and availability compounded by the expectation for stimulants to be effective in ameliorating a broad spectrum of ADHD-related symptoms. Thus, there is an increasing need for treating clinicians to prescribe not only the most effective drug, but also the most appropriate dose with the associated release mechanism and schedule for each ADHD patient presented. In this regard, the field is witnessing an emergence of the personalized medicine approach to ADHD, in which treatment decisions are tailored to each individual. This shift requires a new approach to research into treatment response prediction. Given the heterogeneity of ADHD, a profile of information may be required to capture the most sensitive predictors of treatment response in individuals. These profiles will also benefit from the integration of data from clinical rating scales with more direct measures of cognition and brain function. In conclusion, there is a need to establish a more robust normative framework as the baseline for treatment, as well as diagnostic decisions, and as discussed, the growth of integrated neuroscience databases will be important in this regard.

Attention Deficit Disorder with Hyperactivity↗

Major technology issues in surgical data collection.

Surgical scheduling and data collection is a field that has a long history as well as a bright future. Historically, surgical cases have always involved some amount of data collection. Surgical cases are scheduled and then reviewed. The classic method, that large black surgical log, actually still exists in many hospitals. In fact, there is nothing new about the recording or reporting of surgical cases. If we only needed to record the information and produce a variety of reports on the data, then modern electronic technology would function as a glorified fast index card box--or, in computer database terms, a simple flat file database. But, this is not the future of technology in surgical case management. This article makes the general case for integrating surgical data systems. Instead of reviewing specific software, it essentially addresses the issues of strategic planning related to this important aspect of medical information systems.

Appointments and Schedules↗

Comparison and meta-analysis of microarray data: from the bench to the computer desk.

The upcoming availability of public microarray repositories and of large compendia of gene expression information opens up a new realm of possibilities for microarray data analysis. An essential challenge is the efficient integration of microarray data generated by different research groups on different array platforms. This review focuses on the problems associated with this integration, which are: (1) the efficient access to and exchange of microarray data; (2) the validation and comparison of data from different platforms (cDNA and short and long oligonucleotides); and (3) the integrated statistical analysis of multiple data sets.

Databases, Genetic↗

Absence of an association between serum uric acid and mortality from cardiovascular disease: NIPPON DATA 80, 1980-1994. National Integrated Projects for Prospective Observation of Non-communicable Diseases and its Trend in the Aged.

Although elevated serum uric acid has been associated with an increased risk of cardiovascular disease, its importance as a risk factor is still controversial. The authors examined the relationship between serum uric acid levels and death from all causes, including cardiovascular disease and stroke. The baseline data were collected in the National Cardiovascular Survey in 1980. The survey was carried out for all household members aged 30 years or older in 300 districts, which were randomly selected throughout Japan. The number who participated in the survey was 10,897. The vital status was ascertained in 1994. Finally, 8172 subjects were available for the analyses. There were 108,284 person-years of follow-up, and 960 deaths from all causes, 249 deaths from cardiovascular disease, and 174 deaths from stroke. After adjustment for age and other cardiovascular disease risk factors, uric acid levels were not associated with mortality from all causes, cardiovascular disease, or stroke. These findings indicate that serum uric acid levels are not related to increased risk for death from all causes, including cardiovascular disease and stroke in a Japanese population.

Adult↗

Evaluation of regional left ventricular wall motion with color kinesis: comparison with two-dimensional echocardiography in patients after acute myocardial infarction.

BACKGROUND: Color kinesis (CK) is a new echocardiographic technique for the assessment of left ventricular (LV) wall motion based on acoustic quantification. Using integrated backscatter data, this technique identifies the pixel value transitions from blood to myocardial tissue throughout systole and tracks endocardial motion in real time. The color-encoded images, built on a frame-by-frame basis by adding one color at a time, provide an integrated display of the timing and amplitude of endocardial motion in a single end-systolic frame. Recent studies have shown that CK is a promising clinical tool for quantitative assessment of regional LV function. OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of CK in identifying the regional wall-motion abnormalities diagnosed by conventional two-dimensional (2-D) echocardiography in patients after acute myocardial infarction (AMI). METHODS: The end-systolic color overlays were analyzed using a method to quantify the regional timing and amplitude of endocardial systolic excursion (ESE) based on the count of the numbers of colors. At this point, the total duration (ESE timing) and distance (ESE amplitude) of endocardial excursion from end-diastolic to end-systolic color-frame was calculated in each segment. In 54 patients after AMI, we compared the feasibility and ability of CK superimposed on 2-D superimposed on 2-D superimposed on 2-D echocardiographic images and visual 2-D echo analysis to evaluate the endocardial border excursion in parasternal short-axis (SAX) and apical four-(AP4CH) and two-(AP2CH) chamber views. In 20 normal subjects, the end-systolic color overlays were used to evaluate the variability of the measurements of ESE timing (msec) and amplitude (cm) and to define the reference values. Image quality was considered adequate if at least 12 of 16 segments could be evaluated for systolic function by conventional visual 2-D echo. Among 54 patients, 35 with adequate studies were selected to determine the accuracy of quantitative analysis of CK images in identifying regional wall-motion abnormalities. RESULTS: The SAX view was obtained in 36 of 54 patients; of the possible 216 segments, 210 (97%) were adequately visualized by 2-D echocardiography and 207 (96%) by CK. Apical views were obtained in 50 patients (93%); of the possible 300 segments, 93% were visualized by 2-D echocardiography and 90% by CK in the AP4CH view and 94% and 92%, respectively, were visualized by the two methods in the AP2CH view. In normal subjects, measurements of ESE timing and amplitude were found to be consistent and the mean values were 346 msec (range 280-360) and 0.99 cm (range 0.72-1.26) respectively. In the 35 selected patients, 2-D echocardiography identified 355 normokinetic segments in which ESE timing and amplitude were similar to the reference values. In 83 hypokinetic segments and 108 akinetic segments, ESE timing and amplitude were significantly inferior to values of normokinetic segments (p < 0.001). An ESE timing below the reference values of 280 msec identified all of the 191 asynergic segments (sensitivity and specificity = 100%) and an ESE amplitude of less than 0.70 cm identified 188 asynergic segments (sensitivity = 98% and specificity = 99%). CONCLUSIONS: CK showed good feasibility and diagnostic accuracy in identifying regional wall motion abnormalities in patients with acute myocardial infarction. The model used in our study for the quantitative analysis of color kinesis images, which provided easy and feasible indices of timing and amplitude of endocardial excursion, enabled fast and objective evaluation of LV regional wall motion.

Acute Disease↗

Component plane presentation integrated self-organizing map for microarray data analysis.

We describe a powerful approach, component plane presentation integrated self-organizing map (SOM), for the analysis of microarray data. This approach allows the display of multi-dimensional SOM outputs of microarray data in multiple sample specific presentations, providing distinct advantages in visual inspection of biological significances of genes clustered in each map unit with respect to each RNA sample. Beneficial potentials of the approach are highlighted by processing microarray data from yeast cells as well as human breast malignancies.

Gene Expression Profiling↗

A review of treatment-emergent adverse events during olanzapine clinical trials in elderly patients with dementia.

OBJECTIVE: Olanzapine and other antipsychotics are not approved by the U.S. Food and Drug Administration to treat behavioral disturbances associated with dementia, but they are often prescribed to these patients. Although antipsychotics may be efficacious in this population, elderly patients with dementia may be particularly vulnerable to adverse events. This article reviews the safety of olanzapine in elderly patients with dementia. DATA SOURCES: Data from 6 studies comparing olanzapine to placebo, risperidone, or conventional antipsychotics in elderly patients with dementia were analyzed for mortality, cerebrovascular adverse events (CVAEs), and other adverse events. These trials represent all Lilly olanzapine-comparator trials in this population. The data included integration of 5 double-blind, placebo-controlled studies (olanzapine, N = 1184; placebo, N = 478; median age = 79 years; 1 study also compared olanzapine with risperidone, N = 196) and an open-label study comparing olanzapine (N = 150) with conventional antipsychotics (N = 143). DATA SYNTHESIS: Incidence of mortality was significantly higher in olanzapine- (3.5%) than in placebo-treated patients (1.5%; p = .024). There were no significant differences in the crude incidence of mortality between olanzapine- (2.9%) and risperidone- (2.0%) or olanzapine- (14.8%) and conventional antipsychotic-treated patients (16.1%; p = .871). Risk factors associated with mortality in olanzapine-treated patients included age >/= 80, concurrent benzodiazepine use, treatment-emergent sedation, or treatment-emergent pulmonary conditions. Incidence of CVAEs was approximately 3 times higher in olanzapine- (1.3%) than in placebo-treated patients (0.4%). There were no significant differences in the incidence of CVAEs between olanzapine- (2.5%) and risperidone- (2.0%; p = 1.0) or olanzapine- (3.4%) and conventional antipsychotic-treated patients (4.3%; p = .765). CONCLUSION: These findings should be considered if prescribers elect to treat behavioral disturbances associated with dementia in the elderly with olanzapine or other antipsychotics.

Age Factors↗

Analysis of the role of the leucine zipper motif in regulating the ability of AFAP-110 to alter actin filament integrity.

AFAP-110 has an intrinsic ability to alter actin filament integrity as an actin filament crosslinking protein. This capability is regulated by a carboxy terminal leucine zipper (Lzip) motif. The Lzip motif facilitates self-association stabilizing the AFAP-110 multimers. Deletion of the Lzip motif (AFAP-110(Deltalzip)) reduces the stability of the AFAP-110 multimer and concomitantly increases its ability to crosslink actin filaments, in vitro, and to activate cSrc and alter actin filament integrity, in vivo. We sought to determine how the Lzip motif regulates AFAP-110 function. Substitution of the c-Fos Lzip motif in place of the AFAP-110 Lzip motif (AFAP-110(fos)) was predicted to preserve the alpha-helical structure while changing the sequence. To alter the structure of the alpha-helix, a leucine to proline mutation was generated in the AFAP-110 alpha-helical Lzip motif (AFAP-110(581P)), which largely preserved the sequence. The helix mutants, AFAP-110(Deltalzip), AFAP-110(fos), and AFAP-110(581P), demonstrated reduced multimer stability with an increased capacity to crosslink actin filaments, in vitro, relative to AFAP-110. An analysis of opposing binding sites indicated that the carboxy terminus/Lzip motif can contact sequences within the amino terminal pleckstrin homology (PH1) domain indicating an auto-inhibitory mechanism for regulating multimer stability and actin filament crosslinking. In vivo, only AFAP-110(Deltalzip) and AFAP-110(581P) were to activate cSrc and to alter cellular actin filament integrity. These data indicate that the intrinsic ability of AFAP-110 to crosslink actin filaments is dependent upon both the sequence and structure of the Lzip motif, while the ability of the Lzip motif to regulate AFAP-110-directed activation of cSrc and changes in actin filament integrity in vivo is dependent upon the structure or presence of the Lzip motif. We hypothesize that the intrinsic ability of AFAP-110 to crosslink actin filaments or activate cSrc are distinct functions.

Actin Cytoskeleton↗

Has dopamine a physiological role in the control of sexual behavior? A critical review of the evidence.

The role of dopaminergic systems in the control of sexual behavior has been a subject of study for at least 40 years. Not surprisingly, reviews of the area have been published at variable intervals. However, the earlier reviews have been summaries of published research rather than a critical analysis of it. They have focused upon the conclusions presented in the original research papers rather than on evaluating the reliability and functional significance of the data reported to support these conclusions. During the last few years, important new knowledge concerning dopaminergic systems and their behavioral functions as well as the possible role of these systems in sexual behavior has been obtained. For the first time, it is now possible to integrate the data obtained in studies of sexual behavior into the wider context of general dopaminergic functions. To make this possible, we first present an analysis of the nature and organization of sexual behavior followed by a summary of current knowledge about the brain structures of crucial importance for this behavior. We then proceed with a description of the dopaminergic systems within or projecting to these structures. Whenever possible, we also try to include data on the electrophysiological actions of dopamine. Thereafter, we proceed with analyses of pharmacological data and release studies, both in males and in females. Consistently throughout this discussion, we make an effort to distinguish pharmacological effects on sexual behavior from a possible physiological role of dopamine. By pharmacological effects, we mean here drug-induced alterations in behavior that are not the result of the normal actions of synaptically released dopamine in the untreated animal. The conclusion of this endeavor is that pharmacological effects of dopaminergic drugs are variable in both males and females, independently of whether the drugs are administered systemically or intracerebrally. We conclude that the pharmacological data basically reinforce the notion that dopamine is important for motor functions and general arousal. These actions could, in fact, explain most of the effects seen on sexual behavior. Studies of dopamine release, in both males and females, have focused on the nucleus accumbens, a structure with at most a marginal importance for sexual behavior. Since accumbens dopamine release is associated with all kinds of events, aversive as well as appetitive, it can have no specific effect on sexual behavior but promotes arousal and activation of non-specific motor patterns. Preoptic and paraventricular nucleus release of dopamine may have some relationship to mechanisms of ejaculation or to the neuroendocrine consequences of sexual activity or they can be related to other autonomic processes associated with copulation. There is no compelling indication in existing experimental data that dopamine is of any particular importance for sexual motivation. There is experimental evidence showing that it is of no importance for sexual reward.

Animals↗

Heart specialists incorporate performance improvement measures into EMR.

Midwest Heart Specialists, a physician-owned cardiovascular practice with 55 specialists serving the Chicago area, saved millions of dollars in 2004 on hospitalization costs for patients with coronary artery disease by integrating performance data collection into its existing electronic medical records system.

Benchmarking↗

Chronic venous leg ulcers benefit from surgery: long-term results from 173 legs.

OBJECTIVE: The purpose of this retrospective study was to present 7 years of data from operations of currently active, chronic venous leg ulcers (CEAP: C6), focusing on the short- and long-term effects of healing and recurrence and considering concomitant risk factors. METHODS: Between January 1997 and March 2004, 173 patients (239 legs) with a currently active, chronic venous leg ulcer were surgically treated. The surgical procedures included two main steps: (1) the surgical interruption of reflux in the superficial and perforating veins to reduce venous hypertension in the entire leg and/or the affected area and (2) the surgical procedure involving the ulcer. A total of 123 patients (173 legs) who came to the follow-up were examined. The follow-up period ranged from 3 months to 7 years. The data collection integrated a preoperative examination that included medical history and clinical diagnoses and incorporated measurements such as body mass index, ankle-brachial pressure index, and the neutral position method at the follow-up. The function of the veins was measured with duplex ultrasonography. Finally, the data were analyzed by using various statistical methods, including Kaplan-Meier analysis, Cox regression analysis, and paired t tests. RESULTS: Initially, ulcer healing occurred in 87% of the cases (151 legs). A total of 13% (22 legs) of the venous ulcers never healed, and recurrent venous ulcers occurred in 5% (9 legs). The Kaplan-Meier analyses of ulcer healing showed a healing rate of 85% in 6 months for all legs. The mean time of healing was 1.5 months. Furthermore, the Kaplan-Meier analyses of ulcer recurrence showed a 1.7% rate of recurrence in 6 months for all legs. The 5-year ulcer recurrence rate was 4.6%. The mean time of recurrence was 70.4 months. CONCLUSIONS: On the basis of the results from the 7 years of data from functional surgery of venous leg ulcers and as a result of the outcomes of our study, we recommend surgical treatment of venous leg ulcers at any stage. We therefore conclude that surgery is indicated before an ulcer is intractable to treatment. In general, our findings are based on the understanding and identification of the causes and symptoms of venous ulceration and illustrate that standard surgical methods can be applied for the therapy of venous leg ulcers at any stage.

Adult↗

Privacy and security issues in a wide area health communications network.

In 1993 the first national health information service went live in New Zealand, using commercial network services for all communications. This system provides a point of connection for all health personnel, and for those with a legitimate interest in health care information (e.g. insurers): it also provides access to a number of information resources managed on behalf of the government of New Zealand (e.g. index of health care users), as well as to those developed by individual network service providers. Much of the data exchanged across this network is personalised. Since the recipient may not be known personally to the sender, it is vital that the sender has confidence that the recipient will treat personal information according to agreed criteria for privacy. A Code of Practice covering health information was developed under the New Zealand Privacy Act to ensure that the confidence to share confidential data was supported. For large organisations such as hospitals to function efficiently, they need the flexibility to be able quickly to assign user privileges to selected staff without the need for extra paperwork seeking approval from the centre. But the audit trail requires unique identification of the individual undertaking each transaction. This requirement has been addressed. Some of the data moved across the network relates to life-critical issues, e.g. clinical warnings about allergies or serious medical conditions. A failure of communications causing this vital information to be improperly represented in some way on the receivers system could have disastrous consequences. To ensure the integrity of data transfers, user installations have to be certified compliant with standard test scripts before they are authorized for access to these resources.

Accreditation↗

Genetic toxicology: web resources.

Genetic toxicology is the scientific discipline dealing with the effects of chemical, physical and biological agents on the heredity of living organisms. The Internet offers a wide range of online digital resources for the field of Genetic Toxicology. The history of genetic toxicology and electronic data collections are reviewed. Web-based resources at US National Library of Medicine (NLM), including MEDLINE, PUBMED, Gateway, Entrez, and TOXNET, are discussed. Search strategies and Medical Subject Headings (MeSH) are reviewed in the context of genetic toxicology. The TOXNET group of databases are discussed with emphasis on those databases with genetic toxicology content including GENE-TOX, TOXLINE, Hazardous Substances Data Bank, Integrated Risk Information System, and Chemical Carcinogenesis Research Information System. Location of chemical information including chemical structure and linkage to health and regulatory information using CHEMIDPLUS at NLM and other databases is reviewed. Various government agencies have active genetic toxicology research programs or use genetic toxicology data to assist fulfilling the agency's mission. Online resources at the US Food and Drug Administration (FDA), the US Environmental Protection Agency (EPA), the National Institutes of Environmental Health Sciences, and the National Toxicology Program (NTP) are outlined. Much of the genetic toxicology for pharmaceuticals, industrial chemicals and pesticides that is performed in the world is regulatory-driven. Regulatory web resources are presented for the laws mandating testing, guidelines on study design, Good Laboratory Practice (GLP) regulations, and requirements for electronic data collection and reporting. The Internet provides a range of other supporting resources to the field of genetic toxicology. The web links for key professional societies and journals in genetic toxicology are listed. Distance education, educational media resources, and job placement services are also available online in the field of genetic toxicology. As molecular biology and computational tools improve, new areas within genetic toxicology such as structural activity relationship analysis, mutational spectra databases and toxicogenomics, now have resources online as well.

Animals↗

The mathematical analysis of breath alcohol profiles generated during breath exhalation.

The mathematical analysis of time domain data provides a useful tool for evaluating biological and instrumental systems. Breath alcohol profile measurements generated during exhalation constitute biological signals that can be subjected to a variety of mathematical treatments. The present paper discusses the application of a variety of mathematical procedures to breath alcohol profiles. These mathematical procedures include model approximation, data smoothing, integration, differentiation, and fourier transformation. The different mathematical procedures provide insight into the physiology of breath alcohol measurement and suggest forensic as well as instrumental applications.

Breath Tests↗

PlantSat: a specialized database for plant satellite repeats.

MOTIVATION: Tandemly organized repetitive sequences (satellite DNA) are widespread in complex eukaryotic genomes. In plants, satellite repeats often represent a substantial part of nuclear DNA but only a little is known about the molecular mechanisms of their amplification and their possible role(s) in genome evolution and function. Unfortunately, addressing these questions via characterization of general sequence properties of known satellite repeats has been hindered by a difficulty in obtaining a complete and unbiased set of sequence data for this analysis. This is mainly due to the presence of multiple entries of homologous sequences and of single entries that contain more than one repeated unit (monomer) in the public databases. RESULTS: We have established a computer database specialized for plant satellite repeats (PlantSat) that integrates sequence data available from various resources with supplementary information including repeat consensus sequences, abundances, and chromosomal localizations. The sequences are stored as individual repeat monomers grouped into families, which simplifies their computer analysis and makes it more accurate. Using this feature, we have performed a basic sequence analysis of the whole set of plant satellite repeats with respect to their monomer length and nucleotide composition. The analysis revealed several preferred length ranges of the monomers (approximately 165 bp and its multiples) and an over-representation of the AA/TT dinucleotide in the repeats. We have also detected an enrichment of satellite DNA sequences for the motif CAAAA that is supposed to be involved in breakage-reunion of repeated sequences.

Computational Biology↗

The physiology constant database of teen-agers in Beijing.

Physiology constants of adolescents are important to understand growing living systems and are a useful reference in clinical and epidemiological research. Until recently, physiology constants were not available in China and therefore most physiologists, physicians, and nutritionists had to use data from abroad for reference. However, the very difference between the Eastern and Western races casts doubt on the usefulness of overseas data. We have therefore created a database system to provide a repository for the storage of physiology constants of teen-agers in Beijing. The several thousands of pieces of data are now divided into hematological biochemistry, lung function, and cardiac function with all data manually checked before being transferred into the database. The database was accomplished through the development of a web interface, scripts, and a relational database. The physiology data were integrated into the relational database system to provide flexible facilities by using combinations of various terms and parameters. A web browser interface was designed for the users to facilitate their searching. The database is available on the web. The statistical table, scatter diagram, and histogram of the data are available for both anonym and user according to queries, while only the user can achieve detail, including download data and advanced search.

Adolescent↗

Indicators of impact of services on persons with developmental disabilities: issues concerning data-collection mandates in P.L. 100-146.

Public Law 100-146 requires the Administration on Developmental Disabilities to report to the Congress in 1990 on the status of services to persons with developmental disabilities. Considerable effort has been devoted by the National Association of Developmental Disabilities Councils to providing a national methodology for characterizing state services and for surveying consumer satisfaction with these services; but these data alone will not be sufficient to adequately characterize all variables required by the 1990 report. Definitional, conceptual, and methodological issues related to measurement of scope and extent of services, documenting eligibility and accessibility, and estimating the effectiveness of services was reviewed. A framework was suggested for integrating data-collection with consumer satisfaction survey efforts already underway.

Consumer Behavior↗

Authenticity and integrity of digital mammography images.

Data security becomes more and more important in telemammography which uses a public high-speed wide area network connecting the examination site with the mammography expert center. Generally, security is characterized in terms of privacy, authenticity and integrity of digital data. Privacy is a network access issue and is not considered in this paper. We present a method, authenticity and integrity of digital mammography, here which can meet the requirements of authenticity and integrity for mammography image (IM) transmission. The authenticity and integrity for mammography (AIDM) consists of the following four modules. 1) Image preprocessing: To segment breast pixels from background and extract patient information from digital imaging and communication in medicine (DICOM) image header. 2) Image hashing: To compute an image hash value of the mammogram using the MD5 hash algorithm. 3) Data encryption: To produce a digital envelope containing the encrypted image hash value (digital signature) and corresponding patient information. 4) Data embedding: To embed the digital envelope into the image. This is done by replacing the least significant bit of a random pixel of the mammogram by one bit of the digital envelope bit stream and repeating for all bits in the bit stream. Experiments with digital IMs demonstrate the following. 1) In the expert center, only the user who knows the private key can open the digital envelope and read the patient information data and the digital signature of the mammogram transmitted from the examination site. 2) Data integrity can be verified by matching the image hash value decrypted from the digital signature with that computed from the transmitted image. 3) No visual quality degradation is detected in the embedded image compared with the original. Our preliminary results demonstrate that AIDM is an effective method for image authenticity and integrity in telemammography application.

Computer Security↗